SQA Regulatory Surveillance Summary | October 2020
By Laurel Hacche and Debra Cortner, SQA Associates
ANVISA (Agência Nacional de Vigilância Sanitária)
There were no updates for ANVISA for October 2020.
China Guidances and Regulations
Regulation of Pharmaceutical Production will be Stricter with the Cancellation of Good Manufacturing Practice (GMP) Certification in China, CPhI & P-MEC China, 26 October 2020
The Amendment of the Drug Administration Law of the People’s Republic of China (Draft for Comment) proposes to cancel the GMP certification and Good Supply Practice (GSP) certification. Active Pharmaceutical Ingredients (APIs) and excipients are to be approved together with the pharmaceutical products. Cancellation of the GMP and GSP certification will make it more difficult for pharmaceutical enterprises to compromise workmanship or material or operate illegally. Regulations will also be stricter with cancellation of the GMP and GSP certification. There is strict punishment for data fabrication, resulting in firms being prohibited from engaging in the industry for 10 years. If it is determined that firms have information or data fabrication, their licenses will be revoked. The supervisor directly responsible and other directly responsible personnel will be prohibited from engaging in the industry for 10 years. Personnel who are sentenced to set terms of imprisonment and above due to crimes in terms of pharmaceutical product safety shall not engage in the Research and Development, production, operation, and import and export of pharmaceutical products in their lifetime. If any marketing authorization holder, developing unit, manufacturing enterprise, operating enterprise, or medical institution deliberately commits the offence or has gross negligence, or their offence is serious or causes serious consequences, the directly responsible supervisor and other direct responsible personnel will be fined 30% to 100% of the income obtained from the firm in the previous year. Data fabrication has been seriously investigated in the past three years. Clinical data fabrication must be strictly investigated and heavily punished because pharmaceutical products are a special commodity and any clinical data fabrication may cause health risks to large numbers of people.
The Drug Administration Law will undergo major changes to cancel the GMP certification and legalize the transfer and sales of the pharmaceutical product approval numbers. The China Food and Drug Administration (CFDA) has recently issued the Amendment of the Drug Administration Law of the People’s Republic of China (Draft for Comment), expressed that this amendment surrounded closely the Opinions on Deepening the Reform of the Review and Approval System and Inspiring Innovation of Drugs and Medical Devices issued by the General Office of the Communist Party of China Central Committee and General Office of the State Council of China in October, and proposed 36 reform measures. The Draft for Comment is seen as encouraging innovation, increasing punishment, and moving from stressing threshold to stressing regulation.
The Draft for Comment states that the applicants to obtain pharmaceutical product approval numbers are the marketing authorization holders who may produce and operate pharmaceutical products on their own or delegate the production and operation. “Changing the marketing authorization holder shall comply with conditions specified herein and be approved by the pharmaceutical product administration of the State Council.” This means that the product approval numbers may be transferred according to law, instead of being unmovable as it was previously. However, sales of the approval numbers are legally permitted.
Source/author: Guangzhou Daily / Tu Duanyu
Chinese Regulators Delay Medical Device Unique Device Identification (UDI) Implementation, EMERGO, 14 October 2020
China’s National Medical Products Administration (NMPA) has extended the trial period for its medical device UDI program in response to the coronavirus pandemic, pushing first-round UDI implementation requirement deadlines to early 2021. The NMPA announced that the impact of the COVID-19 public health emergency in China has necessitated pushing back the regulator’s UDI trial period ending date from 01 October 2020 to 01 January 2021.
Expanded List of First-Batch Devices Subject to NMPA UDI Requirements, EMERGO, 14 October 2020
The first batch of medical devices identified by NMPA for UDI requirements comprised Class III high-risk devices. In its announcement on the UDI implementation delay, the regulator has also added device types including in-ear prostheses and spinal interbody fixation/replacement systems to the list of products that must be UDI-compliant by January 2021. Manufacturers and Agents may still enroll in the UDI pilot between now and the January 2021 deadline, according to NMPA.
Therapeutic Goods Administration (TGA)
Information for Sponsors: Supplying Medicines During a Shortage Under Section 19A, TGA Website, 29 September 2020
Section 19A of the Therapeutic Goods Act 1989 allows medicines not currently included in the Australian Register of Therapeutic Goods (ARTG) to be imported into Australia and supplied in place of a registered medicine that is unavailable or in short supply or if relevant registered medicines do not exist but an application for a new medicine is being evaluated by the TGA.
Sponsors can apply for section 19A approval to supply medicines by completing the Section 19A application form. The guidance document, Section 19A: Guidance for Industry, provides detailed information to assist with the application process. Any sponsor can apply to the TGA for approval to supply under section 19A; you do not need to be the sponsor of the registered medicine that is in short supply. To support your application, you will need to provide information on the availability of any registered suitable substitutes for the medicine in shortage. If the registered medicine in shortage is listed on the Pharmaceutical Benefits Scheme (PBS), you are able to apply for listing of the section 19A medicine on the PBS. There are no fees associated with the temporary PBS listing of a section 19A medicine.
The TGA can consider the supply of a medicine under section 19A if it is in the interest of public health and it is approved for general marketing in a foreign country or it is under evaluation for registration on the ARTG. Section 19A approvals are subject to relevant conditions to minimize risks to consumers, granted for a specified period, which usually relates to the period the registered medicine is unavailable or in short supply, and subject to the same pharmacovigilance activities (for example, adverse event reporting and recalls) and advertising restrictions as medicines registered on the ARTG. If the overseas approval is not from one of a list of specified countries, you must provide additional information to confirm that the manufacturing and quality control procedures used in the production of the medicine are acceptable.
Guidance: TGA’s Approach to Delays in Medical Device Conformity Assessment Recertification Due to COVID-19 Pandemic and Delays in EU MDR Implementation, version 1.0, October 2020
The Therapeutic Goods Administration is issuing this guidance to inform sponsors (and, where relevant, manufacturers) about the general approach the TGA will take to the lapsing of conformity assessment documents due to delays in audits due to COVID-19 and the limitations on the current number of notified bodies designated under the European Medical Devices Regulation (MDR). This guidance applies to both overseas and Australian conformity assessment documents. However, where there is a need to distinguish between the two, more specific terms are used. The guidance is not legislative in nature and is subject to the requirements of the therapeutic goods legislation. The exact approach taken by the TGA will depend on the facts of the case and the relevant legislative provisions.
United States Food and Drug Administration (USFDA) – Consent Decrees
FDA Issues First Injunction under Produce Safety Rule to Illinois-based Food Manufacturer for Repeated Food Safety Violations, 15 September 2020
The USFDA announced that Fortune Food Product, Inc., an Illinois-based processor of sprouts and soy products, has agreed to stop production until it, among other things, undertakes remedial action and complies with the Federal Food, Drug, and Cosmetic Act. The action marks the first consent decree of permanent injunction against a firm or grower for violating public safety standards under the Produce Safety Rule enacted under the Food Safety Modernization Act of 2011. The Produce Safety Rule requires, among other things, that covered sprout operations take measures to prevent the introduction of dangerous microbes into seeds or beans used for sprouting; test spent sprout irrigation water (or, in some cases, in-process sprouts) for the presence of certain pathogens; test the growing, harvesting, packing, and holding environment for the presence of the Listeria species or Listeria monocytogenes; and take corrective actions when needed.
This action also follows several inspections conducted by the USFDA, which found that the company failed to comply with Produce Safety and Current Good Manufacturing Practice regulations. In July 2018, the FDA sent a warning letter outlining food safety violations. United States District Judge John Robert Blakey in the U.S. District Court for the Northern District of Illinois entered the consent decree of permanent injunction on 15 September 2020 between the United States and Fortune Food Product, Inc., its majority owner Steven Seeto, and its supervisor Tiffany Jiang. The consent decree prohibits the defendants from growing, harvesting, packing, and holding sprouts and soy products at or from their facility, or any other facility, until certain requirements are met. The consent decree requires the defendants to, among other things, take corrective actions and notify the FDA before such operations may resume.
According to the complaint filed by the United States Department of Justice on behalf of the USFDA, multiple inspections were conducted that documented insanitary conditions showing that sprouts and soy products may have become contaminated with filth or may have been rendered injurious to health. The USFDA is not aware of any confirmed illnesses related to Fortune Food’s products.
USFDA – Pilot Programs
Quality Management Maturity for Finished Dosage Forms Pilot Program for Domestic Drug Product Manufacturers; Program Announcement, 16 October 2020
The USFDA, Center for Drug Evaluation and Research (CDER) is announcing its Quality Management Maturity for Finished Dosage Forms Pilot Program (QMM FDF Pilot Program) for domestic drug product manufacturers of prescription and over-the-counter (OTC) drug products. The purpose of the QMM FDF Pilot Program is to gain insight from third-party assessments of a manufacturer’s quality management system to inform future development of a USFDA rating system to characterize quality management maturity (QMM). Such a rating system would allow a cross-sectional comparison of manufacturers. Manufacturers that choose to disclose their facility ratings could benefit from a competitive advantage, as knowledge of QMM ratings would enable health systems and other purchasers and payers of medications to differentiate between drug manufacturers. This notice invites manufacturers that are interested in participating in the QMM FDF Pilot program to submit a request to participate. The USFDA will accept requests to participate in the QMM FDF Pilot Program through 30 November 2020, and the QMM FDF Pilot Program will run through 31 December 2021.
Quality Management Maturity for Active Pharmaceutical Ingredients Pilot Program for Foreign Facilities; Program Announcement, 16 October 2020
The USFDA, CDER is announcing its Quality Management Maturity for Active Pharmaceutical Ingredients Pilot Program (QMM API Pilot Program) for foreign facilities manufacturing active pharmaceutical ingredients (APIs), including facilities manufacturing drug substance intermediates used to produce APIs, which are used in FDA-regulated prescription and over-the-counter (OTC) drug products. The purpose of the QMM API Pilot Program is to gain insight from third-party assessments of a facility’s quality management system to inform future development of a USFDA rating system to characterize QMM. Such a rating system would allow a cross-sectional comparison of facilities. Facilities that choose to disclose their facility ratings to drug product manufacturers could benefit from a competitive advantage, as knowledge of QMM ratings would enable drug product manufacturers to differentiate between facilities when purchasing APIs. This notice invites foreign facilities that are interested in participating in the QMM API Pilot Program to submit a request to participate. The USFDA will accept requests to participate in the QMM API Pilot Program through 30 November 2020, and the QMM API Pilot Program will run through 31 December 2021.
USFDA – Guidances
Wholesale Distributor Verification Requirement for Saleable Returned Drug Product and Dispenser Verification Requirements When Investigating a Suspect or Illegitimate Product – Compliance Policies; Guidance for Industry, October 2020
On 24 September 2019, the USFDA published the Wholesale Distributor Verification Requirement for Saleable Returned Drug Product – Compliance Policy guidance (the 2019 Compliance Policy), where they announced a one-year delay in enforcement of the requirement for wholesale distributors to verify saleable returned product as required under section 582(c)(4)(D) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360eee-1(c)(4)(D)). The 2019 Compliance Policy explained that the Agency intended to delay enforcement of this requirement until 27 November 2020. This guidance announces the USFDA’s extension of the delay in enforcement. It also sets forth the Agency’s enforcement policy with respect to sections 582(d)(4)(A)(ii)(II) and (d)(4)(B)(iii) of the FD&C Act (21 U.S.C. 360eee-l(d)(4)(A)(ii)(II) and (d)(4)(B)(iii)), which generally provide that, beginning 27 November 2020, a dispenser must verify the product identifier of suspect or illegitimate product in the dispenser’s possession or control.
This guidance addresses the readiness of wholesale distributors to comply with the requirement to verify the product identifier upon receipt of a returned product that the wholesale distributor intends to further distribute under section 582(c)(4)(D) of the FD&C Act. The requirement under section 582(c)(4)(D) of the FD&C Act for wholesale distributors to verify saleable returned products prior to redistribution went into effect on 27 November 2019. The USFDA does not intend to take action against wholesale distributors who do not, prior to 27 November 2023, verify the product identifier prior to further distributing returned product as required under section 582(c)(4)(D) of the FD&C Act. This represents an additional three-year delay from the delay set forth in the 2019 Compliance Policy in enforcement of the requirement for wholesale distributors to verify the product identifier prior to further distributing that returned product.
This guidance also addresses the dispenser requirement in section 582(d)(4)(A)(ii)(II) of the FD&C Act. This provision, which is effective as of 27 November 2020, requires a dispenser to verify whether the product identifier of a suspect product, including the standardized numerical identifier, of at least three packages or 10 percent of such suspect product, whichever is greater, or all packages, if there are fewer than three, corresponds with the product identifier assigned to such product by the manufacturer or repackager. Furthermore, this guidance addresses section 582(d)(4)(B)(iii) of the FD&C Act, which requires dispensers to verify product as described in section 582(d)(4)(A)(ii) of the FD&C Act in response to a notification of illegitimate product from the USFDA or a trading partner. The USFDA does not intend to take action before 27 November 2023 against dispensers who do not verify the product identifiers of suspect product as required by section 582(d)(4)(A)(ii)(II) of the FD&C Act. In addition, the USFDA does not intend to take action before 27 November 2023 against dispensers who do not verify the product identifiers of illegitimate product that are the subject of a notification from the USFDA or a trading partner as required by section 582(d)(4)(B)(iii) of the FD&C Act. This represents a three-year delay in enforcement of the requirements for dispensers to verify the product identifier when investigating suspect or illegitimate product.
USFDA – Recalls
Becton Dickinson CareFusion 303, Inc. Recalls Alaris™ System Pump Module and Pump Module Door Assembly Replacement Kits Due to the Potential for Stuck or Unresponsive Keys, 02 October 2020
Becton Dickinson CareFusion 303, Inc. is recalling the BD Alaris Pump Module and Pump Module Door Assembly Replacement Kits because the keypad may have one or more keys that become unresponsive or stuck. This may lead to an infusion delay or prevent clinicians from changing fluid or medication infusions on the affected devices. For high-risk patients who are receiving life-sustaining infusions, these delays or interruption of infusion can cause serious injury or death. Becton Dickinson has received 976 complaints about this device issue. There have been no reported injuries or deaths.
Marksans Pharma Limited Issues Expansion of Voluntary Nationwide Recall of Metformin Hydrochloride Extended-Release Tablets, USP 500mg & 750mg, Due to the Detection of N-Nitrosodimethylamine (NDMA), 05 October 2020
Marksans Pharma is expanding its initiated recall from 05 June 2020 to include 76 additional unexpired lots of Metformin Hydrochloride Extended-Release Tablets, USP, 500 mg and 750 mg, due to the detection of NDMA levels above the Acceptable Daily Intake Limit (ADI) of 96 ng/day. As of 05 October 2020, the company has not received any reports of adverse events that have been related to this recall. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests.
Sunstar Americas Inc. Issues Voluntary Nationwide Recall of Paroex® Chlorhexidine Gluconate Oral Rinse USP, 0.12% Due to Microbial Contamination, 28 October 2020
Sunstar Americas, Inc. (SAI) is voluntarily recalling Paroex® Chlorhexidine Gluconate Oral Rinse USP, 0.12% products bearing an expiration date from 30 June 2022 to 30 September 2022 to the consumer level. This product may be contaminated with the bacteria Burkholderia lata. Use of the defective product in the immunocompetent host may result in oral and, potentially, systemic infections requiring antibacterial therapy. In the most at-risk populations, the use of the defective product may result in life-threatening infections, such as pneumonia and bacteremia. To date, no adverse events have been reported to SAI related to this recall. The prescription oral rinse product, available through healthcare professionals only, is indicated for use as part of a professional program for the treatment of gingivitis.